PMID- 22933030
OWN - NLM
STAT- MEDLINE
DCOM- 20130419
LR  - 20220310
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 135
IP  - 3
DP  - 2012 Oct
TI  - Metformin in early breast cancer: a prospective window of opportunity neoadjuvant 
      study.
PG  - 821-30
LID - 10.1007/s10549-012-2223-1 [doi]
AB  - Metformin may exert anti-cancer effects through indirect (insulin-mediated) or 
      direct (insulin-independent) mechanisms. We report results of a neoadjuvant 
      "window of opportunity" study of metformin in women with operable breast cancer. 
      Newly diagnosed, untreated, non-diabetic breast cancer patients received 
      metformin 500 mg tid after diagnostic core biopsy until definitive surgery. 
      Clinical (weight, symptoms, and quality of life) and blood [fasting serum 
      insulin, glucose, homeostasis model assessment (HOMA), C-reactive protein (CRP), 
      and leptin] attributes were compared pre- and post-metformin as were terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Ki67 
      scores (our primary endpoint) in tumor tissue. Thirty-nine patients completed the 
      study. Mean age was 51 years, and metformin was administered for a median of 18 
      days (range 13-40) up to the evening prior to surgery. 51 % had T1 cancers, 38 % 
      had positive nodes, 85 % had ER and/or PgR positive tumors, and 13 % had HER2 
      overexpressing or amplified tumors. Mild, self-limiting nausea, diarrhea, 
      anorexia, and abdominal bloating were present in 50, 50, 41, and 32 % of 
      patients, respectively, but no significant decreases were seen on the EORTC30-QLQ 
      function scales. Body mass index (BMI) (-0.5 kg/m(2), p < 0.0001), weight (-1.2 
      kg, p < 0.0001), and HOMA (-0.21, p = 0.047) decreased significantly while 
      non-significant decreases were seen in insulin (-4.7 pmol/L, p = 0.07), leptin 
      (-1.3 ng/mL, p = 0.15) and CRP (-0.2 mg/L, p = 0.35). Ki67 staining in invasive 
      tumor tissue decreased (from 36.5 to 33.5 %, p = 0.016) and TUNEL staining 
      increased (from 0.56 to 1.05, p = 0.004). Short-term preoperative metformin was 
      well tolerated and resulted in clinical and cellular changes consistent with 
      beneficial anti-cancer effects; evaluation of the clinical relevance of these 
      findings in adequately powered clinical trials using clinical endpoints such as 
      survival is needed.
FAU - Niraula, Saroj
AU  - Niraula S
AD  - Division of Medical Oncology and Hematology, Department of Medicine, Mount Sinai 
      Hospital and Princess Margaret Hospital, University of Toronto, 1284-600 
      University Avenue, Toronto, ON M5G 1X5, Canada.
FAU - Dowling, Ryan J O
AU  - Dowling RJ
FAU - Ennis, Marguerite
AU  - Ennis M
FAU - Chang, Martin C
AU  - Chang MC
FAU - Done, Susan J
AU  - Done SJ
FAU - Hood, Nicky
AU  - Hood N
FAU - Escallon, Jaime
AU  - Escallon J
FAU - Leong, Wey Liang
AU  - Leong WL
FAU - McCready, David R
AU  - McCready DR
FAU - Reedijk, Michael
AU  - Reedijk M
FAU - Stambolic, Vuk
AU  - Stambolic V
FAU - Goodwin, Pamela J
AU  - Goodwin PJ
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120830
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Ki-67 Antigen)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Body Mass Index
MH  - Breast Neoplasms/*drug therapy/pathology/*surgery
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Ki-67 Antigen/analysis
MH  - Metformin/administration & dosage/adverse effects/*therapeutic use
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Preoperative Care
MH  - Quality of Life
EDAT- 2012/08/31 06:00
MHDA- 2013/04/23 06:00
CRDT- 2012/08/31 06:00
PHST- 2012/06/07 00:00 [received]
PHST- 2012/08/17 00:00 [accepted]
PHST- 2012/08/31 06:00 [entrez]
PHST- 2012/08/31 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
AID - 10.1007/s10549-012-2223-1 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2012 Oct;135(3):821-30. doi: 10.1007/s10549-012-2223-1. 
      Epub 2012 Aug 30.